We wish to define the pathogenesis of ulcerative colitis, in particular, the mechanism of colonic mucosal injury. The objectives are: (1) to isolate colonic mucosal bound antibodies or immune complexes and define their specificity and role in the disease process, followed by use of these antibodies to identify putative antigens, and (2) to study the secretory IgA status of colonic mucosa in ulcerative colitis and its role in pathogenesis of the disease. By acid elution technique, we have isolated specific antibody bound to colonic mucosa of patients with ulcerative colitis. Initial serologic studies indicate that the antibody is IgG. More antibody will be isolated from colitis colon using protease inhibitors and will be purified by ammonium sulfate precipitation and ion exchange chromatography. The role of the antibody on antibody-dependent cell-mediated colonic epithelial cytolysis will be investigated. In addition, cross-reactivity to bacterial antigens will be performed with fecal anerobes and aerobes. Attempts to identify putative antigens in colonic mucosa will include extraction for soluble antigen(s) including membranes and phenol extracts. Reactivity of the antigens against colitis colon bound-antibody will be investigated by immunodiffusion, immunoelectrophoresis, solid phase microtest radioimmunoassay and affinity chromatography. The secretory IgA system in colonic mucosa will be quantitated by analytical methods including double antibody and solid phase radioimmunoassays. An organ culture system will be developed to study in vitro kinetics of colonic mucosal S-IgA. Secreted proteins will be quantitated by immunoprecipitation and analyzed by electrophoresis on sodium dodecyl sulfate acrylamide gels.